DESCRIPTION: Orientation specificity, or the selective response to bars of light of particular orientations, is a fundamental property of neurons in primary visual cortex (VI). The circuitry underlying the generation of orientation specificity and the map of orientation selective cells remains unsolved. New hypotheses, and recent advances in techniques for studying cortex, give promise of significant new insight into the problem. The investigator proposes the hypothesis that short-range intracortical excitatory synapses, which form the majority of synapses on every cell type in cortex, are critical for generating orientation selectivity. Complementarily, long- range inhibition is crucial for the organization of orientation selective cells into an orientation map. Specific questions he proposes to addresses are as follows. (1) Can thalamic imputs alone to VI neurons generate orientation tuning? (2) How does the development of orientation tuning relate to the development of synaptic transmission in cortex? (3) How does the amplitude and reliability of unitary synaptic transmission develop in VI? (4) How do long-range horizontal connections modulate the strength of excitation and inhibition on individual neurons and on neuronal populations in VI? The investigator proposes that the influence of horizontal connections can be facilitatory or suppressive depending on the relative drive between receptive field center and extraclassical surround. (5) How does the orientation map develop in relation to the development of lateral synaptic transmission and long-range, clustered, connections of neurons in the superficial layers. (6) What roles do specific postsynaptic and presynaptic mediators of activity-dependent development, NMDA receptors and nitric oxide (NO), play in the development of orientation tuning, orientation maps and horizontal connections? These experiments would employ intracellular recording from VI neurons using whole cell techniques in vivo and in slices in vitro, optical imaging of the activity of populations of neurons, and intracellular dye labeling of neuronal morphology. Different approaches would often be used in the same animal, so that cellular and integrative development can be directly correlated.